title: α-Cell loss from islet impairs its insulin secretion in vitro and in vivo.
abstract: Pancreatic islet transplantation is an effective treatment for diabetes mellitus. But it is not clear whether α-cell loss during islets isolation could impair the insulin release from β-cell. To unravel this issue, human islets with α-cell deficiency were prepared by prolonged enzyme digestion, as confirmed by immunocytochemistry, immunofluorescence staining and islet insulin/glucagon content analysis. The functions of islets with α-cell deficiency were evaluated in vitro and in vivo. In vitro, human islets with α-cell deficiency exhibited low glucose-induced insulin release compared with intact islets. In islets deficient in α-cells, exogenous glucagon did not alone stimulate insulin release in the absence of glucose, but increased the glucose-induced insulin release in a dose-dependent manner. In intact islets, glucagon did not significantly change the glucose-stimulated insulin secretion. In vivo, transplantation of human islets with α-cell deficiency did not effectively correct hyperglycemia in diabetic C57BL/6 mice. In diabetic nude mice transplanted with islets deficient in α-cells, administration of exogenous glucagon significantly decreased glycemia, while withdrawing glucagon increased glycemic levels as compared with relevant controls. In addition, the survival of diabetic nude mice grafted with islets deficient in α-cells was significantly shorter than the survival of nude mice grafted with intact islets. These results indicated that glucagon-secreting α-cells have an important role in maintaining glucose-stimulated insulin release from β-cells, and that α-cell loss from islets during isolation has a deleterious effect on insulin secretion.
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.forename: Hanqing
authors.initials: H
authors.lastname: Cai
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.forename: Weiguo
authors.initials: W
authors.lastname: Sui
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery*; D005934:Glucagon / Q000494:pharmacology; D050416:Glucagon-Secreting Cells / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007328:Insulin; D005934:Glucagon